Ovarian cancer ranks fifth in cancer deaths among women and causes more deaths than any other gynecologic malignancy. It is estimated that in the United States 22,430 new cases will be diagnosed each year with 15,280 deaths. Ovarian carcinoma remains enigmatic in at least two important respects. First, the histological region of origin for this cancer remains obscure and second, an identifiable premalignant lesion that is generally recognized by cancer pathologists is yet to be defined. The majority (80%) of patients present with advanced stage disease with cancer cells throughout the abdominal cavity, leading directly to the high mortality (5 year survival rates 15-45%). In contrast, the survival rate for early stage disease, with malignancy confined to the ovary, is about 95%.
The median overall survival for patients with advanced ovarian cancer has improved from approximately 1 year in 1975 to currently in excess of 3 years. For subsets of patients having optimally debulked disease and receiving treatment with taxane- and platinum-based combination chemotherapy, survival now exceeds 5 years. However the disease course is one of remission and relapse requiring intermittent re-treatment. The presence of cancer cells in effusions within the serosal (peritoneal, pleural, and pericardial) cavities is a clinical manifestation of advanced stage cancer and is associated with poor survival. Tumor cells in effusions most frequently originate from primary carcinomas of the ovary, breast, and lung, and from malignant mesothelioma, a native tumor of this anatomic site. Unlike the majority of solid tumors, particularly at the primary site, cancer cells in effusions are not amenable to surgical removal and failure in their eradication is one of the main causes of treatment failure.
PCT WO2011/057034 suggests that serosal ovarian cancer stem cells (also called catena cells), which possess a glycocalyx (pericellular coat), may be the most drug resistant structure in ovarian cancer. Presumably due to the impermeability of the glycocalyx, catena cells appear resistant to many chemotherapeutic agents. It is important to discover compounds that can penetrate the glycocalyx and exert toxicity against ovarian cancer stem cells. Eradicating cancer stem cells (CSCs) would be expected to increase the efficiency of therapy for ovarian or other serosal cancers, including metastatic serosal cancer.